Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

Abstract

G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.

Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate

“…Single-stranded oligos were used in structure characterization of G-quadruplexes for three reasons. First, G-quadruplexes often play a regulatory role in molecular processes where DNA is single-stranded, such as replication, transcription, and repair (Dolinnaya et al 2016). Second, single-strandedness allows better characterization of quadruplex formation and thus is most often used in experimental studies (Dailey et al 2010).…”

The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

“…Our study has shown that besides cellular uptake neutrophil functions can also be modulated by G-quadruplex topology. It should be noted that just telomere G-quadruplexes could adopt a broad range of folding patterns [20,70].…”

“…The core of the G-quadruplex consists of two or more stacked planar G-tetrads, in which four guanine bases from different G-tracts interact via Hoogsteen bonding, while the intervening sequences are extruded as loops. DNA and RNA G-quadruplexes are the only non-canonical structures whose presence within genomes was strictly proved [20,21]. Being structural elements of the genome, G-quadruplexes are recognized by numerous proteins and enzymes, whose activity is modulated by these non-canonical DNA structures.…”

“…On the other hand, G-quadruplex formation causes genome instability (inversions, recombination, mutations, deletions, etc.) associated with oncological diseases and neurological disorders [20].…”

Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate

“…Single-stranded oligos were used in structure characterization of G-quadruplexes, for three reasons. First, G-quadruplexes often play a regulatory role in molecular processes where DNA is single-stranded, such as replication, transcription, and repair 72 . Second, single-strandedness allows better characterization of quadruplex formation and thus is most often used in experimental studies 73 .…”